Author(s): Luke Jackson
Mentor(s): Jeffery S. Tessem
Institution BYU
The function and health of pancreatic beta cells are critical in regulating blood glucose levels and are significantly influenced by the cellular lipid environment. Elevated free fatty acids (FFAs), such as palmitate and oleate that are associated with obesity and type 2 diabetes, affect beta cell function, survival, and gene expression. We examined the differential effects of the saturated fatty acid palmitate and the monounsaturated fatty acid oleate on beta cell gene expression. Using RNA sequencing, we quantified gene expression changes in the INS-1 rat beta cell lines treated with palmitate or oleate under standard culture conditions. Bioinformatics analysis revealed that palmitate treatment upregulated genes involved in apoptosis and endoplasmic reticulum stress pathways, consistent with its known lipotoxic effects. In contrast, oleate treatment was associated with upregulation of genes involved in lipid metabolism and mitochondrial function, suggesting a more protective or adaptive response. Notably, genes involved in insulin secretion were differentially regulated between treatments, indicating distinct impacts on beta cell function. We hypothesize that palmitate and oleate differentially regulate gene expression in beta cells, with palmitate promoting stress and apoptotic pathways, while oleate upregulates genes associated with lipid metabolism and cellular adaptation. These findings underscore the role of specific fatty acid types in modulating beta cell gene expression and highlight potential targets for therapeutic intervention to protect beta cell health in metabolic disorders. Further research will investigate the long-term effects of chronic FFA exposure on beta cell function and the interplay between palmitate and oleate in mixed-lipid environments.